Browsing by Author "Chung, Jihae"
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Item Inhibition of Calcium Oxalate Monohydrate Crystallization Using Organic Growth Modifiers(2013-05) Chung, Jihae; Rimer, Jeffrey D.; Robertson, Megan L.; Miljanić, Ognjen Š.Inhibition of calcium oxalate monohydrate (COM), the most common component in human kidney stone diseases, was investigated using various structural derivatives of citrate, a known inhibitor of COM crystallization. Bulk crystallization studies revealed the specific binding of modifiers to COM crystal surfaces. Kinetic studies were performed to quantify both the efficacy and potency of growth inhibitors. These studies demonstrated that increased number of hydroxyl and carboxyl groups play a crucial role in interacting with specific COM crystal surface. Designing effective inhibitors require a fundamental understanding of modifier-crystal interactions at the molecular level. Consequently, we have used in situ AFM to observe the COM surface growth in the absence and in the presence of a growth inhibitor. Results obtained in this study may serve as a general platform to investigate the molecular recognition between modifiers and COM crystal surfaces as a step towards designing preventative drugs for kidney stone disease.Item Role of Polyprotic Acids as Inhibitors of Calcium Oxalate Crystallization(2017-05) Chung, Jihae; Rimer, Jeffrey D.; Vekilov, Peter G.; Robertson, Megan L.; Miljanić, Ognjen Š.; Reynolds, Michael A.Crystallization is a ubiquitous phenomenon in many synthetic, natural, and biological systems that is often mediated by the action of foreign molecules (or modifiers) to tune the physicochemical properties of crystalline materials. Pathological biomineralization is an example of an undesirable crystallization process where modifiers act as inhibitors to reduce the rate of crystal growth. Here, we focus on the effects of modifiers and parametric studies of the growth medium on the crystallization of calcium oxalate monohydrate (COM), which is the most prevalent constituent of human kidney stones. We performed a systematic study to observe the specificity and efficacy of polyprotic organic acids, including the current drug citrate and its structural analogues, on COM crystallization. Interestingly, we identified modifiers that exhibit different modes of inhibitory action. A notable example is that of hydroxycitrate, which induces dissolution of the crystal surface in highly supersaturated growth solutions. Combined results from in situ atomic force microscopy studies and density functional theory calculations support our hypothesis that modifier-crystal interactions induce localized strain on the crystal lattice, which, in turn, leads to surface dissolution. We also studied the effects of solute and modifier speciation on COM crystallization under varying solution alkalinity that encompasses physiological conditions. We observe a pronounced disparity in the efficacy of modifiers with solution alkalinity owing to changes in local supersaturation near the crystal surface. Collectively, the improved fundamental understanding of modifier-crystal interactions coupled with high-resolution characterization techniques serve as a platform to developing new therapeutics for kidney stone disease as well as elucidating the role of natural biomolecules in the pathological biomineralization of calcium oxalate stones.